HU224822B1 - Naphthalene derivatives as prostaglandin i2 agonists, pharmaceutical compns. contg. them and process for preparing them - Google Patents
Naphthalene derivatives as prostaglandin i2 agonists, pharmaceutical compns. contg. them and process for preparing them Download PDFInfo
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- HU224822B1 HU224822B1 HU9602466A HU9602466A HU224822B1 HU 224822 B1 HU224822 B1 HU 224822B1 HU 9602466 A HU9602466 A HU 9602466A HU 9602466 A HU9602466 A HU 9602466A HU 224822 B1 HU224822 B1 HU 224822B1
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- 238000004519 manufacturing process Methods 0.000 title claims description 49
- 239000000556 agonist Substances 0.000 title claims description 5
- 150000002790 naphthalenes Chemical class 0.000 title description 11
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 title 1
- 229960001123 epoprostenol Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 144
- 150000003839 salts Chemical class 0.000 claims abstract description 105
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- 239000001257 hydrogen Substances 0.000 claims abstract description 34
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 26
- 229910052736 halogen Chemical group 0.000 claims abstract description 25
- 150000002367 halogens Chemical group 0.000 claims abstract description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 22
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 10
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 7
- -1 (trans) -2- [5- (Carboxymethoxy) -2-hydroxy-1,2,3,4-tetrahydro-1-naphthyl] ethyl N, N-diphenylcarbamate sodium salt Chemical compound 0.000 claims description 207
- 238000000034 method Methods 0.000 claims description 98
- 238000002360 preparation method Methods 0.000 claims description 46
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 159000000000 sodium salts Chemical class 0.000 claims description 8
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 4
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 3
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- CQCXTGQFFXIHJE-AREMUKBSSA-N 2-[[(6R)-6-hydroxy-6-[(2-methylphenyl)-phenylcarbamoyl]oxy-7,8-dihydro-5H-naphthalen-1-yl]oxy]acetic acid Chemical compound CC1=C(C=CC=C1)N(C(O[C@]1(CC2=CC=CC(=C2CC1)OCC(=O)O)O)=O)C1=CC=CC=C1 CQCXTGQFFXIHJE-AREMUKBSSA-N 0.000 claims description 2
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- 125000006267 biphenyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 claims description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 4
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- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 claims 1
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- CWTHYRLIHFJZQS-UHFFFAOYSA-N ethyl 2-[[6-[2-(diphenylcarbamoyloxy)ethyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetate Chemical compound C1CC=2C(OCC(=O)OCC)=CC=CC=2CC1CCOC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 CWTHYRLIHFJZQS-UHFFFAOYSA-N 0.000 description 1
- HLEGMPPAZCJEBV-UHFFFAOYSA-N ethyl 2-[[6-hydroxy-6-[(2-methylphenyl)-phenylcarbamoyl]oxy-7,8-dihydro-5H-naphthalen-1-yl]oxy]acetate Chemical compound CC1=C(C=CC=C1)N(C(OC1(CC2=CC=CC(=C2CC1)OCC(=O)OCC)O)=O)C1=CC=CC=C1 HLEGMPPAZCJEBV-UHFFFAOYSA-N 0.000 description 1
- YESCESVKVQMOAR-UHFFFAOYSA-N ethyl 5-[tert-butyl(diphenyl)silyl]oxy-3,4-dihydronaphthalene-2-carboxylate Chemical compound C=12CCC(C(=O)OCC)=CC2=CC=CC=1O[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 YESCESVKVQMOAR-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
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- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
- 102000045360 human SDHB Human genes 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 229960002240 iloprost Drugs 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- LPVPIHAVUIQSCD-JTQLQIEISA-N methyl (2s)-5-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxylate Chemical compound C1=CC=C(OC)C2=C1C[C@@H](C(=O)OC)CC2 LPVPIHAVUIQSCD-JTQLQIEISA-N 0.000 description 1
- JCMGIIXJAJCQOI-UHFFFAOYSA-N methyl 2-[[6-[(benzhydryloxycarbonylamino)methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetate Chemical compound C1CC=2C(OCC(=O)OC)=CC=CC=2CC1CNC(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 JCMGIIXJAJCQOI-UHFFFAOYSA-N 0.000 description 1
- VRBYTGXNLHOTKU-UHFFFAOYSA-N methyl 2-[[6-[[benzhydryloxycarbonyl(methyl)amino]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetate Chemical compound C1CC=2C(OCC(=O)OC)=CC=CC=2CC1CN(C)C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 VRBYTGXNLHOTKU-UHFFFAOYSA-N 0.000 description 1
- SYSOKGIHVDGFTR-UHFFFAOYSA-N methyl 5-methoxy-3,4-dihydronaphthalene-2-carboxylate Chemical compound C1=CC(OC)=C2CCC(C(=O)OC)=CC2=C1 SYSOKGIHVDGFTR-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
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- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
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- 201000008383 nephritis Diseases 0.000 description 1
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- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- GNRSAWUEBMWBQH-UHFFFAOYSA-N oxonickel Chemical compound [Ni]=O GNRSAWUEBMWBQH-UHFFFAOYSA-N 0.000 description 1
- JIWAALDUIFCBLV-UHFFFAOYSA-N oxoosmium Chemical compound [Os]=O JIWAALDUIFCBLV-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical class [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/02—Compounds containing any of the groups, e.g. carbazates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/14—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/16—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by esterified hydroxyl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Epoxy Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9404734A GB9404734D0 (en) | 1994-03-10 | 1994-03-10 | Heterocyclic compounds |
| GB9407036A GB9407036D0 (en) | 1994-04-08 | 1994-04-08 | Naphthalene derivatives |
| PCT/JP1995/000373 WO1995024393A1 (en) | 1994-03-10 | 1995-03-08 | Naphthalene derivatives as prostaglandin i2 agonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| HU9602466D0 HU9602466D0 (en) | 1996-11-28 |
| HUT75226A HUT75226A (en) | 1997-04-28 |
| HU224822B1 true HU224822B1 (en) | 2006-02-28 |
Family
ID=26304472
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU9602466A HU224822B1 (en) | 1994-03-10 | 1995-03-08 | Naphthalene derivatives as prostaglandin i2 agonists, pharmaceutical compns. contg. them and process for preparing them |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US5763489A (enExample) |
| EP (1) | EP0749424B1 (enExample) |
| JP (1) | JP3245864B2 (enExample) |
| KR (1) | KR100383305B1 (enExample) |
| CN (1) | CN1057522C (enExample) |
| AT (1) | ATE205479T1 (enExample) |
| AU (1) | AU688871B2 (enExample) |
| CA (1) | CA2185104A1 (enExample) |
| DE (1) | DE69522676T2 (enExample) |
| DK (1) | DK0749424T3 (enExample) |
| ES (1) | ES2160156T3 (enExample) |
| GR (1) | GR3037080T3 (enExample) |
| HU (1) | HU224822B1 (enExample) |
| PT (1) | PT749424E (enExample) |
| RU (1) | RU2155188C2 (enExample) |
| TW (1) | TW282456B (enExample) |
| WO (1) | WO1995024393A1 (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2179399A1 (en) * | 1993-12-20 | 1995-06-29 | Kiyoshi Taniguchi | 4,5-diaryloxazole derivatives |
| TW401408B (en) | 1995-07-21 | 2000-08-11 | Fujisawa Pharmaceutical Co | Heterocyclic compounds having prostaglandin I2 agonism |
| DE19537548A1 (de) * | 1995-10-09 | 1997-04-10 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
| DE19604191A1 (de) * | 1996-02-06 | 1997-08-07 | Hoechst Schering Agrevo Gmbh | 2,4-Diamino-1,3,5-triazine, Verfahren zu deren Herstellung und deren Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| AUPO713297A0 (en) * | 1997-06-02 | 1997-06-26 | Fujisawa Pharmaceutical Co., Ltd. | Oxazole compound |
| GB9720270D0 (en) | 1997-09-25 | 1997-11-26 | Pharmagene Lab Limited | Medicaments for the treatment of migraine |
| AUPP003297A0 (en) | 1997-10-27 | 1997-11-20 | Fujisawa Pharmaceutical Co., Ltd. | 4,5-diaryloxazole compounds |
| AUPP029197A0 (en) * | 1997-11-10 | 1997-12-04 | Fujisawa Pharmaceutical Co., Ltd. | Benzocycloheptene derivatives |
| AUPP109097A0 (en) | 1997-12-22 | 1998-01-22 | Fujisawa Pharmaceutical Co., Ltd. | Napthalene derivatives |
| US6335459B1 (en) | 1998-12-23 | 2002-01-01 | Syntex (U.S.A.) Llc | Aryl carboxylic acid and aryl tetrazole derivatives as IP receptor modulators |
| CN1370079A (zh) * | 1999-06-21 | 2002-09-18 | 藤泽药品工业株式会社 | 皮肤溃疡治疗剂 |
| US20040127529A1 (en) * | 1999-06-21 | 2004-07-01 | Fujisawa Pharmaceutical Co., Ltd. | Remedies for skin ulcer |
| WO2002042243A1 (fr) * | 2000-11-21 | 2002-05-30 | Fujisawa Pharmaceutical Co., Ltd | Processus de preparation de derives de tetrahydronaphtalene |
| JPWO2002085412A1 (ja) * | 2001-04-18 | 2004-08-05 | 藤沢薬品工業株式会社 | 組織線維化抑制剤 |
| US20060217421A1 (en) | 2003-05-09 | 2006-09-28 | Hajimu Kurumatani | Fortifier |
| TWI417095B (zh) | 2006-03-15 | 2013-12-01 | Janssen Pharmaceuticals Inc | 1,4-二取代之3-氰基-吡啶酮衍生物及其作為mGluR2-受體之正向異位性調節劑之用途 |
| PL2094662T3 (pl) | 2006-12-14 | 2012-09-28 | Astellas Pharma Inc | Związki oparte na policyklicznych kwasach użyteczne jako antagoniści rCRTH2 oraz jako środki przeciwalergiczne |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| EP2203439B1 (en) | 2007-09-14 | 2011-01-26 | Ortho-McNeil-Janssen Pharmaceuticals, Inc. | 1',3'-disubstituted-4-phenyl-3,4,5,6-tetrahydro-2h, 1'h-ý1, 4'¨bipyridinyl-2'-ones |
| EP2280696B9 (en) | 2008-03-18 | 2015-12-09 | Arena Pharmaceuticals, Inc. | Modulators of the prostacyclin (pgi2) receptor useful for the treatment of disorders related thereto |
| MX2011002042A (es) | 2008-09-02 | 2011-06-20 | Ortho Mcneil Janssen Pharm | Derivados de 3-azabiciclo[3.1.o]hexilo como moduladores de los receptores del glutamato metabotropico. |
| WO2010060589A1 (en) | 2008-11-28 | 2010-06-03 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors |
| EP2430022B1 (en) | 2009-05-12 | 2013-11-20 | Janssen Pharmaceuticals, Inc. | 1,2,4-Triazolo[4,3-a]pyridine derivatives and their use for the treatment or prevention of neurological and psychiatric disorders |
| JP5707390B2 (ja) | 2009-05-12 | 2015-04-30 | ジャンセン ファーマシューティカルズ, インコーポレイテッド | 1,2,4−トリアゾロ[4,3−a]ピリジン誘導体およびmGluR2受容体の正のアロステリック調節因子としてのその使用 |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| WO2012062750A1 (en) | 2010-11-08 | 2012-05-18 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| CA2814998C (en) | 2010-11-08 | 2019-10-29 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| ME03518B (me) | 2014-01-21 | 2020-04-20 | Janssen Pharmaceutica Nv | Kombinacije koje obuhvataju pozitivne alosterične modulatore ili ortosterične agoniste metabotropnog glutamatergičnog receptora podtipa 2 i njihova primjena |
| AU2015208233B2 (en) | 2014-01-21 | 2019-08-29 | Janssen Pharmaceutica Nv | Combinations comprising positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic receptor subtype 2 and their use |
| CN110582271B (zh) | 2017-03-01 | 2022-06-14 | 阿瑞那制药公司 | 包含pgi2受体激动剂的组合物及其制备方法 |
| AU2023222747A1 (en) | 2022-02-15 | 2024-08-22 | United Therapeutics Corporation | Crystalline prostacyclin (ip) receptor agonist and uses thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1366514A1 (ru) * | 1986-01-28 | 1988-01-15 | Днепропетровский химико-технологический институт им.Ф.Э.Дзержинского | Способ получени производных N-арил-5-ариламидо-4,6-диметилпиридона-2 |
| DE3837809A1 (de) * | 1988-11-08 | 1990-05-10 | Merck Patent Gmbh | Tetralinderivate |
| US5344836A (en) * | 1991-11-11 | 1994-09-06 | Ono Pharmaceutical Co., Ltd. | Fused benzeneoxyacetic acid derivatives |
-
1995
- 1995-03-08 JP JP52335695A patent/JP3245864B2/ja not_active Expired - Fee Related
- 1995-03-08 CA CA002185104A patent/CA2185104A1/en not_active Abandoned
- 1995-03-08 US US08/702,546 patent/US5763489A/en not_active Expired - Fee Related
- 1995-03-08 PT PT95910763T patent/PT749424E/pt unknown
- 1995-03-08 RU RU96120174/04A patent/RU2155188C2/ru not_active IP Right Cessation
- 1995-03-08 ES ES95910763T patent/ES2160156T3/es not_active Expired - Lifetime
- 1995-03-08 HU HU9602466A patent/HU224822B1/hu not_active IP Right Cessation
- 1995-03-08 DK DK95910763T patent/DK0749424T3/da active
- 1995-03-08 AT AT95910763T patent/ATE205479T1/de not_active IP Right Cessation
- 1995-03-08 TW TW084102192A patent/TW282456B/zh active
- 1995-03-08 CN CN95192846A patent/CN1057522C/zh not_active Expired - Fee Related
- 1995-03-08 DE DE69522676T patent/DE69522676T2/de not_active Expired - Fee Related
- 1995-03-08 WO PCT/JP1995/000373 patent/WO1995024393A1/en not_active Ceased
- 1995-03-08 KR KR1019960704963A patent/KR100383305B1/ko not_active Expired - Fee Related
- 1995-03-08 AU AU18618/95A patent/AU688871B2/en not_active Ceased
- 1995-03-08 EP EP95910763A patent/EP0749424B1/en not_active Expired - Lifetime
-
1998
- 1998-02-23 US US09/028,861 patent/US5863918A/en not_active Expired - Fee Related
-
2001
- 2001-10-31 GR GR20010401952T patent/GR3037080T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| KR970701698A (ko) | 1997-04-12 |
| US5763489A (en) | 1998-06-09 |
| DE69522676D1 (de) | 2001-10-18 |
| DK0749424T3 (da) | 2001-11-26 |
| JP3245864B2 (ja) | 2002-01-15 |
| AU688871B2 (en) | 1998-03-19 |
| RU2155188C2 (ru) | 2000-08-27 |
| HU9602466D0 (en) | 1996-11-28 |
| PT749424E (pt) | 2002-03-28 |
| HUT75226A (en) | 1997-04-28 |
| CN1057522C (zh) | 2000-10-18 |
| ATE205479T1 (de) | 2001-09-15 |
| DE69522676T2 (de) | 2002-04-18 |
| EP0749424B1 (en) | 2001-09-12 |
| WO1995024393A1 (en) | 1995-09-14 |
| ES2160156T3 (es) | 2001-11-01 |
| EP0749424A1 (en) | 1996-12-27 |
| JPH09509958A (ja) | 1997-10-07 |
| KR100383305B1 (ko) | 2003-11-01 |
| AU1861895A (en) | 1995-09-25 |
| TW282456B (enExample) | 1996-08-01 |
| HK1013289A1 (en) | 1999-08-20 |
| CN1147250A (zh) | 1997-04-09 |
| CA2185104A1 (en) | 1995-09-14 |
| US5863918A (en) | 1999-01-26 |
| GR3037080T3 (en) | 2002-01-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of definitive patent protection due to non-payment of fees |